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Substance P evokes cation currents through TRP channels in HEK293 cells
E J Oh1, T D Gover, R Cordoba-Rodriguez
1Pharmacology and Experimental Therapeutics, University of Maryland Medical School, Baltimore, Maryland 21201-1559, USA.
Journal of Neurophysiology
|September 11, 2003
Summary
Tachykinin receptor NK2R activation signals Transient Receptor Potential Channels (TRPC). Substance P induced cation currents in cells expressing both NK2R and TRPC, suggesting TRPC mediates SP effects in sensory neurons.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Signaling
Background:
- Tachykinin receptors (NK1R, NK2R, NK3R) activation leads to increased intracellular calcium ([Ca2+]i) via Gq/G11, phospholipase C (PLC), and membrane depolarization.
- Tachykinins depolarize neurons by reducing K+ currents or activating non-specific cation currents (Icat).
- Transient Receptor Potential Channels (TRPC) are non-specific cation channels activated by [Ca2+]i in a PLC-dependent manner.
Purpose of the Study:
- To investigate whether the NK2R can signal through TRPC channels.
- To determine if Substance P (SP) can induce cation currents via NK2R-TRPC interaction.
Main Methods:
- Whole-cell patch-clamp recordings in HEK293 cells.
- HEK293 cells stably expressing human TRP3 channels (TRP3C) and transiently expressing NK2R-EGFP were used.
- Application of Substance P (SP) and an NK2R-specific antagonist (SR48968).
Main Results:
- Bath application of SP (1 microM) induced an Icat in cells co-expressing TRP3C and NK2R.
- The SP-induced Icat peaked within 3 minutes and was blocked by SR48968.
- The reversal potential (Erev) of the SP current indicated a non-specific cation channel.
- Icat was not observed in cells expressing only TRP3C or only NK2R.
Conclusions:
- NK2R can be functionally coupled to TRP channels in HEK293 cells.
- SP-induced cation currents in vagal primary sensory neurons may be mediated by TRPC channels.